20-17494045-T-G

Position:

• chr20-17494045-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001195.5(BFSP1):​c.*29A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,560,820 control chromosomes in the GnomAD database, including 211,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19166 hom., cov: 33)
  • Exomes 𝑓: 0.52 (192600 hom.)
• Consequence: BFSP1 NM_001195.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0530

Genes affected

BFSP1 (HGNC:1040): (beaded filament structural protein 1) This gene encodes a lens-specific intermediate filament-like protein named filensin. The encoded protein is expressed in lens fiber cells after differentiation has begun. This protein functions as a component of the beaded filament which is a cytoskeletal structure found in lens fiber cells. Mutations in this gene are the cause of autosomal recessive cortical juvenile-onset cataract. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-17494045-T-G is Benign according to our data. Variant chr20-17494045-T-G is described in ClinVar as [Benign]. Clinvar id is 1283614.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP1	NM_001195.5	c.*29A>C		3_prime_UTR_variant	8/8	ENST00000377873.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP1	ENST00000377873.8	c.*29A>C		3_prime_UTR_variant	8/8	1	NM_001195.5	P1
BFSP1	ENST00000377868.6	c.*29A>C		3_prime_UTR_variant	8/8	1
BFSP1	ENST00000536626.7	c.*29A>C		3_prime_UTR_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76167 AN: 151952 Hom.: 19135 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.515

GnomAD3 exomes AF: 0.522 AC: 117578 AN: 225236 Hom.: 31028 AF XY: 0.522 AC XY: 63300 AN XY: 121190

Gnomad AFR exome AF: 0.443

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.560

Gnomad EAS exome AF: 0.468

Gnomad SAS exome AF: 0.562

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.524

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.521 AC: 734369 AN: 1408750 Hom.: 192600 Cov.: 26 AF XY: 0.522 AC XY: 364947 AN XY: 698578

Gnomad4 AFR exome AF: 0.448

Gnomad4 AMR exome AF: 0.570

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.559

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.501 AC: 76243 AN: 152070 Hom.: 19166 Cov.: 33 AF XY: 0.502 AC XY: 37342 AN XY: 74344

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.512

Alfa AF: 0.526 Hom.: 21095

Bravo AF: 0.502

Asia WGS AF: 0.518 AC: 1805 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6105762; hg19: chr20-17474690; COSMIC: COSV64900539;